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PHAR222 > L12 Neuroendocrine Hormones > Flashcards

L12 Neuroendocrine Hormones Flashcards

1
Q

The endocrine system regulates many of the body’s activities:

A

growth; reproduction; adaption to stress; immunity; metabolic activity; glucose homeostasis; circulatory volume; Ca2+ homeostasis

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2
Q

Endocrine activities are produced by endogenous chemical messengers, called _____ which are secreted from endocrine glands.

A

endocrine hormones

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3
Q

Several major hormones are members of the neuroendocrine system, in which hormone release is regulated by the_____

A

brain

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4
Q

Parts of the endocrine system

A

The female ovaries, male testes, and pituitary, thyroid, and adrenal glands are major constituents of the endocrine system

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5
Q

Neuroendocrine anatomy

A
  • [pictures on slides] pituitary glands underneath brain. It is attached to the hypothalamus via a stalk.
  • Mainly the hypothalamus and the pituitary gland
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6
Q

Releasing factors/peptides

A

GnRH; GHRH; TRH; CRH Somatostatin (GIR)

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7
Q

Tropic hormones

A

ACTH; GH; FSH; LH; TSH; PRL

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8
Q

ACTH

A
  • Adrenocorticotropic hormone (ACTH)
  • tropic hormone produced by the A.pituitary.
  • The hypothalamic-pituitary axis controls it.
  • ACTH regulates cortisol and androgen production. (glucocorticoids and mineralcorticoids)
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9
Q

GH

A
  • growth hormone
  • growth promotion: lipids and carbohydrate metabolism
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10
Q

FSH + LH

A
  • growth of reproductive system
  • sex hormones
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11
Q

TSH

A
  • Thyroid Stimulating Hormone
  • produced by the pituitary gland.
  • regulate (stimulate) production of thyroid hormones by the thyroid gland.
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12
Q

PL

A
  • prolactin
  • milk production
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13
Q

Neuroendocrine system is diagram

A

Neural tissue
↓ RF
Endocrine system
↓ blood (tropic hormone)
Endocrine tissue/ gland
↓ blood (effector hormone). ⥀ negative feedback
Target organs/tissues
↓
Physiological response

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14
Q

Drugs (pharmacology) vs hormone

A

{slides}

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15
Q

Thyroxine hormone (gland/effect/release)

A
  • thyroid
  • Brain development; digestion; increase metabolic activity
  • TSH
  • part of hypothalamic pituitary axis
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16
Q

Insulin-like growth factor (gland/effect/release)

A
  • liver
  • Growth and metabolism
  • GH
  • hypothalamic pituitary axis
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17
Q

Cortisol (gland/effect/release)

A
  • Adrenals
  • Adaptation to stress; immunomodulation
  • ACTH
  • part of hypothalamic pituitary axis
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18
Q

Sec steroids (gland/effect/release)

A
  • Testes; ovaries; placenta
  • Reproduction; secual characteristics
  • LH, FSH
  • hypothalamic pituitary axis
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19
Q

Insulin (gland/effect/release)

A
  • pancreas
  • availability of glucose to cells
  • blood glucose levels
20
Q

Hormone release is stimulated by hypothalamic _____ ____ and pituitary trophic hormones, which regulate effector hormone_____ and actions

A

releasing factors
production

21
Q

Neuroendocrine system: example of hormone release

A

Physiologic input from the brain
↓
Hypothalamus
↓ Releasing hormone (e.g. GHRH, TRH)
↓
Pituitary gland
↓ Trophic hormone (e.g. GH, TSH)
Endocrine gland
↓ Effector hormone (e.g. IGF-1, T4)
Target organ →Effect (e.g. growth, increased metabolic rate)

22
Q

[Negative feedback control] inhibited by the endocrine hormone which exerts negative feedback effects on the____ to inhibit release of releasing and_____ hormones.

A

HPA
trophic

23
Q

Negative feedback control diagram

A

Physiologic input from the brain
↓
Hypothalamus ⬅︎ inhibit
↓. Releasing hormone
Pituitary gland ⬅︎ inhibit
↓. Trophic hormone
Endocrine gland
↓. Effector hormone ⬆︎Neg feedback
Target organ⤍Effect

24
Q

What inhibits growth hormone –> insulin-like growth factors

A

Somatostatin

25
Thyrotropin releasing hormone (TRH) ↓ Thyrotropin ↓ What effector hormones
Thyroxine (T4 & T3)
26
Hormone deficiency [hypothyroidism or type I diabetes:]
requires exogenous hormone replacement due to lack of endogenous production or receptor defect
27
Hormone excess [e.g. acromegaly (tumour): ]
requires endocrine surgery or inhibitors of hormone release or action to combat excess levels
28
Hormone supplementation [e.g. type II diabetes, or corticosteroid therapy for immune suppression: ]
exogenous hormone (or analogs) administered to amplify effect
29
Hormone suppression [pituitary suppression (for IVF) or contraception: ]
achieved by exogenous hormones to maintain negative feedback
30
Growth Hormone (GH) info (Choh Hao Li)
* secretion is stimulated by GHRH & inhibited by somatostatin * secretion is also stimulated by deep sleep, especially in children * secretion is highest in the newborn and during puberty, falling dramatically with adulthood and ageing * 191 aa peptide, most abundant of the pituitary hormones
31
Effects of GH
* The major effect of GH is to stimulate normal proportional growth. * It does this by stimulating the production by the liver of insulin-like growth factor-1 (IGF-1) * IGF-1 (70 aa) stimulates protein synthesis (esp. in skeletal muscle), bone growth and cartilage synthesis
32
Effects of GH diagram
Hypothalamus ↓ (+) ↓ (-) GHRH Somatostatin ↓ Anterior pituitary ↓ Growth hormone (somatropin) ↓ ↓ ↓ Liver ↓ ↓ ↓ IGF-1 ↓ Muscle, bone, etc Feedback on slide
33
______ which is identical to GH and produced by recombinant DNA technology
Somatropin
34
Control of GH levels
* Negative feedback mechanisms – GH inhibits GHRH release – IGF-1 inhibits GH release and stimulates somatostatin release * for tight control over GH and IGF-1 release (and actions) * loss of this tight control of GH production can lead to – lack of growth (dwarfism) – excess growth (giantism, acromegaly)
35
loss of this tight control of GH production can lead to
– lack of growth (dwarfism) – excess growth (giantism, acromegaly)
36
Growth Hormone Deficiency → Dwarfism
* Somatropin used to achieve satisfactory growth in dwarfism caused by low GH production * not useful if dwarfism is caused by a lack of GH receptors - **Laron dwarfism** or lack of IGF-1 (**African pygmies**) – use human IGF-1 instead
37
Normal GH
Anterior pituitary ↓ Growth Hormone ↓ ↓ ↓ Liver ↓ ↓ ↓ IGF-1 ↓ Normal growth
38
Hypopituitary dwarfism diagram due to pituitary gland tumor or genetic factors
↓ Anterior pituitary function ↓ ↓ Growth Hormone ↓ ↓ ↓ Liver ↓ ↓ ↓ ↓ IGF-1 ↓ Reduced growth
39
GH excess → Giantism / Acromegaly E.g. Pituitary gland tumor
↑ Anterior pituitary function ↓ ↑ Growth Hormone ↓ Liver ↓ ↑ IGF-1 ↓ Enhanced growth
40
Acromegaly
* generally caused by a benign pituitary tumour and increased GH * enlargement mainly of the facial structures, and hands and feet * ↑ death rate (av. life span<10 years) due to higher rates of cardiovascular & lung disease, diabetes, etc. (not cancer)
41
Overview of acromegaly treatment
* Surgery → ↓tumor * Somatostatin Analogues → ↓GH release * GH- receptor antagonist → ↓GH actions * objective is to reduce IGF-1 levels, as elevated levels of IGF-1 are linked to higher death rates.
42
Treatment of Acromegaly [surgery]
* surgery = 1st line treatment (50% success rate) – then radiation to remove lingering tumor cells (slow response) * if surgery is not effective then the release of GH & IGF-1 may be inhibited by somatostatin analogues
43
Treatment of Acromegaly [somatostatin analogues]
* if surgery not effective then the release of GH & IGF-1 inhibited by somatostatin analogues (60-80% success rate) * octreotide/lanreotide (s.c. injection 2-3 times daily/ monthly) * **pasireotide** (pan SST receptor agonist, ↑ response rate)
44
pasireotide
* somatostatin analog * SST receptor agonist, * inhibition of ACTH secretion (not on slide)
45
Treatment of Acromegaly [GH- rec antagonist]
* **pegvisomant** GH receptor antagonist (>90% success)
46
Growth hormone receptor activation
* GH is a 191 amino acid protein * GH binds to 2 cell-surface GH receptors, resulting in receptor dimerization and activation (enzyme-linked receptor) * GH receptor activation --> enhanced IGF-1 expression
47
GH receptor blockade (Pegvisomant)
* mutant GH molecule * single amino acid substitution (Gly for Arg at position 120), * aa disrupts the binding to the 2nd GH receptor & prevents GH receptor dimerization & activation. * Pegvisomant (PEG) stops dimerisation → no receptor activation → No IGF-1 production

PHAR222 (26 decks)

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